Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos AiresBuenos Aires, Argentina.
Instituto de Investigaciones en Microbiología y Parasitología Médica, CONICET, Universidad de Buenos AiresBuenos Aires, Argentina.
Front Cell Infect Microbiol. 2017 Sep 8;7:398. doi: 10.3389/fcimb.2017.00398. eCollection 2017.
Reactive arthritis (ReA) is an inflammatory condition of the joints that arises following an infection. enterocolitis is one of the most common infections leading to ReA. Although the pathogenesis remains unclear, it is known that IL-17 plays a pivotal role in the development of ReA. IL-17-producers cells are mainly Th17, iNKT, and γδT lymphocytes. It is known that iNKT cells regulate the development of Th17 lineage. Whether iNKT cells also regulate γδT lymphocytes differentiation is unknown. We found that iNKT cells play a protective role in ReA. BALB/c Jα18 mice suffered a severe enterocolitis, a 3.5-fold increase in IL-17 expression and aggravated inflammation of the synovial membrane. On the other hand, activation of iNKT cells with α-GalCer abrogated IL-17 response to enterocolitis and prevented intestinal and joint tissue damage. Moreover, the anti-inflammatory effect of α-GalCer was related to a drop in the proportion of IL-17-producing γδT lymphocytes (IL17-γδTcells) rather than to a decrease in Th17 cells. In summary, we here show that iNKT cells play a protective role against -enterocolitis and -induced ReA by downregulating IL17-γδTcells.
反应性关节炎（ReA）是一种关节炎症，在感染后发生。肠炎是导致 ReA 的最常见感染之一。尽管发病机制尚不清楚，但已知 IL-17 在 ReA 的发展中起关键作用。IL-17 产生细胞主要是 Th17、iNKT 和 γδT 淋巴细胞。已知 iNKT 细胞调节 Th17 谱系的发育。iNKT 细胞是否也调节 γδT 淋巴细胞分化尚不清楚。我们发现 iNKT 细胞在 ReA 中起保护作用。BALB/c Jα18 小鼠患有严重的肠炎，IL-17 表达增加了 3.5 倍，滑膜炎症加重。另一方面，用 α-GalCer 激活 iNKT 细胞可阻断肠炎对 IL-17 的反应，并防止肠道和关节组织损伤。此外，α-GalCer 的抗炎作用与 IL-17 产生 γδT 淋巴细胞（IL17-γδT 细胞）比例下降有关，而与 Th17 细胞减少无关。总之，我们在这里表明，iNKT 细胞通过下调 IL17-γδT 细胞在对抗 - 肠炎和 - 诱导的 ReA 中发挥保护作用。
